rs150384171

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 5P and 4B. PS3PM4_SupportingBS2

The NM_016579.4(CD320):c.262_264delGAG(p.Glu88del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,606,154 control chromosomes in the GnomAD database, including 102 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,other (no stars). ClinVar reports functional evidence for this variant: "SCV004105179: Fibroblast cells from patients apparently homozygous for the CD320 c.262_264del (p.Glu88del) variant showed reduced uptake of holo-transcobalamin (holo-TC) as well as elevated levels of homocysteine and methylmalonic acid in culture medium (Quadros et al. 2010. PubMed ID: 20524213" and additional evidence is available in ClinVar.

Frequency

Genomes: 𝑓 0.0080 ( 7 hom., cov: 33)

Exomes 𝑓: 0.011 ( 95 hom. )

Consequence

CD320
NM_016579.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity; other criteria provided, conflicting classifications P:3U:2B:4O:1

Conservation

PhyloP100: 0.450

Publications

16 publications found

Variant links:

Genes affected

CD320 (HGNC:16692): (CD320 molecule) This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

CD320 Gene-Disease associations (from GenCC):

methylmalonic acidemia due to transcobalamin receptor defect
Inheritance: AR, Unknown Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

CD320 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PS3

PS3 evidence extracted from ClinVar submissions: SCV004105179: Fibroblast cells from patients apparently homozygous for the CD320 c.262_264del (p.Glu88del) variant showed reduced uptake of holo-transcobalamin (holo-TC) as well as elevated levels of homocysteine and methylmalonic acid in culture medium (Quadros et al. 2010. PubMed ID: 20524213; Pangilinan et al. 2022. PubMed ID: 35107211).

PM4

Nonframeshift variant in NON repetitive region in NM_016579.4. Strenght limited to Supporting due to length of the change: 1aa.

BS2

High Homozygotes in GnomAd4 at 7 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	NM_016579.4	MANE Select	c.262_264delGAG	p.Glu88del	conservative_inframe_deletion	Exon 2 of 5	NP_057663.1	Q9NPF0-1
	CD320	NM_001165895.2		c.143-949_143-947delGAG		intron	N/A	NP_001159367.1	Q9NPF0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD320	ENST00000301458.10	TSL:1 MANE Select	c.262_264delGAG	p.Glu88del	conservative_inframe_deletion	Exon 2 of 5	ENSP00000301458.4	Q9NPF0-1
CD320	ENST00000596002.5	TSL:1	n.665_667delGAG		non_coding_transcript_exon	Exon 2 of 5	ENSP00000471773.1	M0R1C4
CD320	ENST00000596002.5	TSL:1	n.665_667delGAG		3_prime_UTR	Exon 2 of 5	ENSP00000471773.1	M0R1C4

Frequencies

GnomAD3 genomes

AF:

0.00803

AC:

1216

AN:

151518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00293

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0124

Gnomad SAS

AF:

0.00271

Gnomad FIN

AF:

0.00315

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00673

GnomAD2 exomes

AF:

0.00936

AC:

2299

AN:

245504

AF XY:

0.00905

show subpopulations

Gnomad AFR exome

AF:

0.00236

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.00437

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00837

GnomAD4 exome

AF:

0.0110

AC:

15935

AN:

1454522

Hom.:

AF XY:

0.0107

AC XY:

7730

AN XY:

723916

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

33452

American (AMR)

AF:

0.0140

AC:

625

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00965

AC:

252

AN:

26116

East Asian (EAS)

AF:

0.0102

AC:

405

AN:

39674

South Asian (SAS)

AF:

0.00322

AC:

278

AN:

86216

European-Finnish (FIN)

AF:

0.00372

AC:

175

AN:

47026

Middle Eastern (MID)

AF:

0.00111

AC:

AN:

5384

European-Non Finnish (NFE)

AF:

0.0121

AC:

13470

AN:

1111696

Other (OTH)

AF:

0.0108

AC:

649

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

868

1736

2604

3472

4340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00802

AC:

1216

AN:

151632

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

586

AN XY:

74058

show subpopulations

African (AFR)

AF:

0.00292

AC:

121

AN:

41368

American (AMR)

AF:

0.0137

AC:

208

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.0125

AC:

AN:

5136

South Asian (SAS)

AF:

0.00271

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00315

AC:

AN:

10486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0105

AC:

713

AN:

67848

Other (OTH)

AF:

0.00666

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00830

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0101

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity; other

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Methylmalonic acidemia due to transcobalamin receptor defect (4)

not provided (5)

CD320-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.45

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over